A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps - The BiRCh Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 288
- 试验地点
- 100
- 主要终点
- Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24
研究概览
简要总结
The primary purpose of the study is to evaluate the efficacy of brensocatib at 10 and 40 milligrams (mg) once daily (QD) compared with placebo in improving clinical symptoms of CRSsNP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who have at least a 12-week history before Screening Visit of CRSsNP and confirmed by endoscopy at Visit 1 (Screening).
- •Participants must have a NCS of ≥2 at Visit 1 (Screening Visit) and Visit 2 (Baseline; average score in the week prior to randomization).
- •Participants must have sTSS (nasal congestion [NC], anterior/posterior rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (Screening) and at Visit 2 (Baseline; average score in the week prior to randomization).
- •Participants who have at least 1 of the 3 following features:
- •Previous sinonasal surgery for CRS, including but not limited to fenestrated endoscopic sinus surgery and balloon sinuplasty.
- •Received medical treatment with systemic corticosteroids (SCS) to treat symptoms of CRS as defined by any dose and duration within 1 year of Screening Visit or intolerance/contraindication to SCS.
- •Received a course of antibiotics to treat symptoms of CRS within 1 year before the Screening Visit.
- •Participants who have a blood eosinophil count ≤750 cells/microliter (μL) at Visit 1 (Screening).
- •Participants who have bilateral inflammation of paranasal sinuses in the CT scan performed during Screening and bilateral ethmoid and/or maxillary opacification before randomization as confirmed by the central reader.
- •Participants who have a SNOT-22 score of ≥20 at Visit 1 (Screening) and Visit 2 (Baseline).
- •Participants who have received a stable daily dose regimen of MFNS for at least 4 weeks before Visit 2 (Baseline).
排除标准
- •Diagnosis of unilateral or bilateral chronic rhinosinusitis with nasal polyps (CRSwNP).
- •Clinical diagnosis of cystic fibrosis (CF) or primary ciliary dyskinesia.
- •Scheduled sinus surgery at any time during the study.
- •Participants who have had nasal surgery within 4 weeks before Visit 1 (Screening) and during the Screening Period.
- •Significant oral maxillofacial structural abnormalities or severe septal deviation.
- •Participants with radiological suspicion or confirmed invasive fungal rhinosinusitis, odontogenic sinusitis, osteomas, or nasal tumors.
- •Participants with acute change in symptoms consistent with acute rhinosinusitis.
- •Participants with seasonal allergic rhinitis whose symptoms coincide with the treatment period of the study.
- •Participants with moderate to severe atopic dermatitis requiring treatment with high potency topical steroids or topical calcineurin inhibitors or biologics.
- •Clinical diagnosis of Papillon-Lefèvre syndrome.
- •Note: Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Brensocatib 40 mg
Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Brensocatib (Drug)
Brensocatib 40 mg
Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Mometasone furoate nasal spray (MFNS) (Drug)
Brensocatib 10 mg
Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Brensocatib (Drug)
Brensocatib 10 mg
Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Mometasone furoate nasal spray (MFNS) (Drug)
Placebo
Participants will receive a brensocatib-matching placebo tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Placebo (Drug)
Placebo
Participants will receive a brensocatib-matching placebo tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
干预措施: Mometasone furoate nasal spray (MFNS) (Drug)
结局指标
主要结局
Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24
时间窗: Baseline and Week 24
次要结局
- Percentage of Participants who Experienced at Least One Adverse Event (AE)(Up to 28 weeks)
- Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at Week 24(Baseline and Week 24)
- Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24(Baseline and Week 24)
- Proportion of Participants Requiring Rescue (Antibiotics, Systemic Corticosteroids [SCS], and/or Nasal Surgery) due to Worsening of any Chronic Rhinosinusitis (CRS) Symptoms up to Week 24(Baseline up to Week 24)
- Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24(Baseline and Week 24)
- Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24(Baseline and Week 24)
- Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24(Baseline and Week 24)
- Plasma Concentration of Brensocatib(Pre-dose and at multiple timepoints post-dose up to Week 24)